Understanding the clinical course of perinatally acquired HIV infection among adolescents and preadolescents, and the consequences of fetal and neonatal exposure to HIV and antiretroviral chemotherapy among a representative cohort of children in the United States presents a unique scientific opportunity. Recognizing this opportunity, the National Institutes of Child Health and Human Development (NICHD) intends to establish the Pediatric HIV/AIDS Cohort Study (PHACS) to conduct research among two cohorts: A cohort of perinatally infected adolescents and preadolescents (age 7-18) will be established to evaluate the impact of HIV and ART on sexual maturation, pubertal development, and socialization, and a drug toxicity surveillance system among perinatally HIV exposed uninfected children will evaluate long-term effects of in-utero ART exposure. PHACS will be comprised of a Scientific Leadership Group (SLG), a Data and Operations Center (DOC), and up to 20 PHACS Clinical Investigator Sites. The Departments of Epidemiology and the Center for Biostatistics in AIDS Research (CBAR) at the Harvard School of Public Health, Westat and Frontier Science will collaborate to form the PHACS DOC. In addition to collaborating to define the PHACS research agenda, during year 1 the PIs will provide methodological support for the development of all PHACS analytic projects, develop the (base and uninfected) core protocols, develop and support an active CAB, write and manage a site solicitation, establish site sub-contracts, obtain and merge all preexisting data bases from previous cohorts (PACTG 219/219C, WITS, PSD), and plan and conduct all LG and full PHACS Network Meetings. In years 2-5, they will continue to provide design, methodological, and analytical expertise and support to the development of PHACS research protocols;and train and monitor sites in proper procedures for PHACS research. Together, HSPH/CBAR, Westat and Frontier Science bring long histories of providing the type of methodological and operational support required by the PHACS, as well as innovative methods to enhance and maximize the efficiency of PHACS study design, conduct, and analysis. Given their prior and current professional experience, the PIs expect to be uniquely positioned to provide the scientific and epidemiologic leadership to successfully conduct the PHACS.